NM_002811.5:c.617T>G

Variant names:

• chr16-74305375-T-G
• rs2034187215
• NM_002811.5:c.617T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002811.5(PSMD7):​c.617T>G​(p.Leu206Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PSMD7 NM_002811.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14
• Publications: 0 publications found

Genes affected

PSMD7 (HGNC:9565): (proteasome 26S subunit, non-ATPase 7) The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 17. [provided by RefSeq, Jul 2008]

PDPR2P (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2641638).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002811.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD7	NM_002811.5	MANE Select	c.617T>G	p.Leu206Arg	missense	Exon 7 of 7	NP_002802.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PSMD7	ENST00000219313.9	TSL:1 MANE Select	c.617T>G	p.Leu206Arg	missense	Exon 7 of 7	ENSP00000219313.4	P51665
	PSMD7	ENST00000937729.1		c.524T>G	p.Leu175Arg	missense	Exon 6 of 6	ENSP00000607788.1
	PSMD7	ENST00000937730.1		c.506T>G	p.Leu169Arg	missense	Exon 7 of 7	ENSP00000607789.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	23
DANN	Benign	0.89
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.099
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.12	N
PhyloP100		6.1
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	1.7	N
REVEL	Benign	0.23
Sift	Benign	1.0	T
Sift4G	Benign	0.84	T
Polyphen		0.0	B
Vest4		0.75
MutPred		0.41		Gain of MoRF binding (P = 0.0021)
MVP		0.22
MPC		0.66
ClinPred		0.64	D
GERP RS		5.7
Varity_R		0.78
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2034187215; hg19: chr16-74339273;